Protein Synthesis Initiation in Bacteria

Abstract

Ribosomes are responsible for translating the information in messenger ribonucleic acids (mRNAs) to synthesise proteins that the cell needs to carry out its function. Protein synthesis begins with the 30S ribosomal subunit recruiting a mRNA with the help of an initiator transfer RNA and three initiation factors. Successful recruitment of the mRNA results in the formation of the 30S pre‐initiation complex, which is followed by the joining of the 50S ribosomal subunit to form the 70S ribosome. Recent studies indicate the order in which the initiation factors bind and promote the steps in initiation complex formation. The formation of the pre‐initiation/initiation complex is often the rate‐limiting step during the process of translation, as it is influenced by a number of translational regulatory mechanisms. As a result, the process of initiation can play a significant role in gene expression.

Key Concepts:

  • Translation initiation is a key step for regulating gene expression.

  • Initiation factors 1, 2 and 3 are essential proteins that promote the binding of the initiator tRNA to the 30S subunit P site and the joining of the 50S subunit.

  • Initiation factors 1, 2 and 3 are critical for the positioning the mRNA in the correct reading frame for translation.

  • Efficient requirement of mRNA by the 30S subunit depends on the Shine–Dalgarno sequence in the mRNA forming base pairs with the anti‐Shine–Dalgarno sequence located at the 3′‐end of 16S rRNA.

  • Kinetic studies have shown the order in which initiation factors bind to the 30S subunit.

  • Cryo‐EM and crystallographic work have revealed the three‐dimensional location of initiation factors on the 30S subunit and the 70S ribosome.

Keywords: initiation factors; translation; Shine–Dalgarno sequence; ribosome; mRNA; tRNA

Figure 1.

The final stages of translation termination followed by the subsequent steps involved in the formation of the translation initiation complex. Step 1: dissociation of 70S ribosome into 50S subunit (grey) and 30S subunit (cyan) by ribosome recycling factor (RRF in red) and elongation factor G (EF‐G in yellow); step 2: binding of IF3 in magenta and IF2 in green to the 30S subunit; step 3: binding of IF1 in blue; step 4: binding of fMet‐tRNAfMet (orange linear object); step 5: binding of mRNA (red curved line); step 6: unfolding of mRNA; step 7: interaction of fMet‐tRNAfMet with the mRNA start codon in the P site; step 8: binding of the 50S subunit to the 30S pre‐initiation complex; step 9: dissociation of IF1, IF2 and IF3 from the 70S ribosome.

Figure 2.

Location of initiation factors on 30S ribosomal subunit. The crystal structure of the 30S subunit (cyan) with mRNA (violet) and P site tRNA (orange). The head, beak, shoulder, cleft, body, spur and platform of the 30S subunit are marked to aid orientation. The structures of IF1 (blue), IF2 (green) and IF3 (magenta). The cartoon shows the approximate location of the fMet‐tRNAfMet in the P site and IF1, IF2 and IF3 on the 30S subunit.

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Grunberg‐Manago, Marianne, Studer, Sean M, and Joseph, Simpson(Aug 2014) Protein Synthesis Initiation in Bacteria. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000542.pub3]